Toluene

CAS RN:108-88-3

Health Effects

0.2.1 SUMMARY OF EXPOSURE

0.2.1.1 ACUTE EXPOSURE

A) USES: Toluene (toluol, methyl benzene) is an aromatic petroleum hydrocarbon that has many commercial and industrial applications. It is used as a solvent and starting material for organic synthesis and is found in paints, paint thinners, glues, and other products. Toluene products are abused via inhalation for their intoxicating effects.

B) TOXICOLOGY: It has long been held that toluene's effect on the central nervous system are via nonspecific lipophilic membrane interactions, which in turn modulates several neurotransmitter systems (ie, dopamine, acetylcholine, GABA, glycine, and serotonin).

C) EPIDEMIOLOGY: Exposures are common, but significant toxicity is generally only seen in the setting of deliberate inhalation abuse and deaths are rare.

D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Acute ingestion causes CNS depression, oropharyngeal and gastric pain and vomiting. Splash exposure to eyes may cause irritation, burning, blepharospasm, conjunctivitis, corneal edema, and corneal abrasions. Symptoms usually resolve within 48 hours. Prolonged or repeated dermal exposures may result in a defatting dermatitis. Occupational exposure has been linked to an increased risk of esophageal and rectal cancers as well as increased mortality from bone and connective tissue cancers.

2) SEVERE TOXICITY: Acute inhalation produces a biphasic response with an initial CNS excitation followed by CNS depression, which is characterized by ataxia, fatigue, sedation, occasionally seizures, and at very high concentrations general anesthesia. Sudden death may occur from hypoxia or cardiac dysrhythmias. Chronic inhalational abuse is associated with muscular weakness, gastrointestinal symptoms (pain, nausea, vomiting), renal tubular acidosis (hypokalemia and metabolic acidosis), hepatic injury, and neuropsychiatric symptoms. Patients who chronically abuse toluene may exhibit hypokalemia, hematuria, proteinuria, oliguria, paresis, rhabdomyolysis, hallucinations, hyperactive reflexes, peripheral neuropathy, personality changes, tremors, headaches, emotional lability, and memory loss. Patients with long-term inhalational abuse may develop progressive irreversible encephalopathy with cognitive difficulty and cerebellar ataxia. Significant inhalational exposure causes an easily recognized odor to the breath that may persist for several days after exposure ceases. There are a small number of case reports of mothers who regularly abused toluene recreationally during pregnancy giving birth to children with microcephaly, CNS dysfunction, and minor head, face and limb anomalies. However, some of these mothers also abused ethanol as well.

A) Multiple physical deformities, with signs similar to fetal alcohol syndrome, microencephaly, CNS dysfunction, and variable growth deficiencies, have occurred in infants born to mothers who abused toluene during pregnancy.

0.2.21 CARCINOGENICITY

0.2.21.1 IARC CATEGORY

A) IARC Carcinogenicity Ratings for CAS108-88-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Toluene

b) Carcinogen Rating: 3

1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

0.2.21.2 HUMAN OVERVIEW

A) A link between toluene exposure and esophageal and rectal cancers, increased mortality from bone and connective tissue cancers, and one case of non-Hodgkin lymphoma has been suggested but not confirmed.

B) The International Agency for Research on Cancer (IARC) has described toluene as Group 3 (not classifiable as to its carcinogenicity in humans).

0.2.21.3 ANIMAL OVERVIEW

A) Animal data have been limited and equivocal.

0.2.22 GENOTOXICITY

A) Chromosome damage has been linked to exposure to toluene. There is conflicting information regarding the potential of toluene to cause DNA strand breaks, and regarding its mutagenicity.

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